Moderate, little, or no improvements in neurobehavioral symptoms among individuals with long COVID: A 34-country retrospective study

(1) Background: Some people with COVID-19 develop a series of symptoms that last for several months after infection, known as Long COVID. Although these symptoms interfere with people’s daily functioning and quality of life, few studies have focused on neurobehavioral symptoms and the risk factors associated with their development; (2) Methods: 1001 adults from 34 countries who had previously tested positive for COVID-19 completed the Neurobehavioral Symptom Inventory reporting the symptoms before their COVID-19 diagnosis, during the COVID-19 infection, and currently; (3) Results: Participants reported large-sized increases before vs. during COVID-19 in all domains. Participants reported a medium-sized improvement (during COVID-19 vs. now) in somatic symptoms, a small-sized improvement in affective symptoms, and very minor/no improvement in cognitive symptoms. The risk factors for increased neurobehavioral symptoms were: being female/trans, unemployed, younger age, low education, having another chronic health condition, greater COVID-19 severity, greater number of days since the COVID-19 diagnosis, not having received oxygen therapy, and having been hospitalized. Additionally, participants from North America, Europe, and Central Asia reported higher levels of symptoms across all domains relative to Latin America and Sub-Saharan Africa; (4) Conclusions: The results highlight the importance of evaluating and treating neurobehavioral symptoms after COVID-19, especially targeting the higher-risk groups identified. General rehabilitation strategies and evidence-based cognitive rehabilitation are needed in both the acute and Long COVID phases.Daniela Ramos Usuga was supported by a predoctoral fellowship from the Basque Government (PRE_2019_1_0164)

The Impact of Sleep, Physical Activity and Sedentary Behaviour on Symptoms of Depression and Anxiety Before and During the COVID-19 Pandemic in a Sample of South African Participants

During lockdowns associated with the COVID-19 pandemic, individuals have experienced poor sleep quality and sleep regularity, changes in lifestyle behaviours, and heightened depression and anxiety. However, the inter-relationship and relative strength of those behaviours on mental health outcomes is still unknown. We collected data between 12 May and 15 June 2020 from 1048 South African adults (age: 32.76 ± 14.43 years; n = 767 female; n = 473 students) using an online questionnaire. Using structural equation modelling, we investigated how insomnia symptoms, sleep regularity, exercise intensity/frequency and sitting/screen-use (sedentary screen-use) interacted to predict depressive and anxiety-related symptoms before and during lockdown. We also controlled for the effects of sex and student status. Irrespective of lockdown, (a) more severe symptoms of insomnia and greater sedentary screen-use predicted greater symptoms of depression and anxiety and (b) the effects of sedentary screen-use on mental health outcomes were mediated by insomnia. The effects of physical activity on mental health outcomes, however, were only significant during lockdown. Low physical activity predicted greater insomnia symptom severity, which in turn predicted increased depressive and anxiety-related symptoms. Overall, relationships between the study variables and mental health outcomes were amplified during lockdown. The findings highlight the importance of maintaining physical activity and reducing sedentary screen-use to promote better sleep and mental health

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

The impact of primary dysmenorrhoea on pain perception, quality of life, and sleep in young healthy women.

Primary dysmenorrhoea, or painful menstruation in the absence of pelvic pathology, is a common, and often debilitating, gynaecological condition that affects between 45 to 95% of menstruating women. Despite the high prevalence, dysmenorrhoea is often poorly treated, and even disregarded, by health professionals, pain researchers, and the women themselves, who may accept it as a normal part of the menstrual cycle. The overall purpose of this thesis is two-fold: first, to contribute knowledge about the impact and consequences of recurrent severe menstrual pain on pain sensitivity, mood, quality of life and sleep in women with primary dysmenorrhoea, and secondly, to investigate day-time and night-time treatment of recurrent primary dysmenorrhoeic pain. For this thesis, I completed five separate studies on three different groups of young, otherwise healthy women with a history of severe primary dysmenorrhoea, and age-matched controls without dysmenorrhoea. The first two studies, presented in Chapter 2, addressed the question of whether women with primary dysmenorrhoea are hypersensitive to experimental pain. I used clinically-relevant experimentally-induced muscle pain stimuli (intramuscular injection of hypertonic saline and ischaemia) in referred and non-referred sites of menstrual pain, at different phases of the menstrual cycle. Women with dysmenorrhoea, compared to women without dysmenorrhoea, had increased sensitivity to deep-muscle pain both within the area of referred menstrual pain and at a remote pain-free site. Further, the increased muscle pain sensitivity was evident even in phases of the menstrual cycle when women did not have menstrual pain, illustrating that the changes in pain perception extend outside of the painful menstruation phase. These findings suggest that women with dysmenorrhoea show long-lasting changes in pain processing possibly because of the recurrent dysmenorrhoeic pain. A secondary aim of the study presented in Chapter 2a, was to determine the impact of menstrual cycle phase on experimentally-induced muscle pain sensitivity in women with and without primary dysmenorrhoea. My results suggest that menstrual cycle phase has no effect on pain sensitivity in either group of women. As part of my studies, I investigated the impact of dysmenorrhoeic pain on quality of life and mood. I found that women with dysmenorrhoea had a significantly reduced quality of life (Chapter 3) and poorer mood (Chapter 2a and Chapter 5), during menstruation compared to their pain-free follicular phase, and compared to the menstruation phase of the pain-free control women. These data highlight the negative impact that primary dysmenorrhoea has on young women, for up to a few days every month. Non-steroidal anti-inflammatory drugs (NSAIDs) are often prescribed as the first-line therapy for menstrual pain. Yet, severe dysmenorrhoeic pain is often poorly managed, especially at night, when the pain likely disrupts sleep. I conducted two studies investigating the effectiveness of diclofenac potassium, a readily-available NSAID with a low side-effect profile, compared to placebo, in alleviating severe primary dysmenorrhoeic pain across the day (Chapter 4), and during the night (Chapter 5). I also investigated the effectiveness of diclofenac potassium in improving subjective and objective sleep quality (Chapter 5). I found that the daily recommended dose (150 mg) of diclofenac potassium, administered at three timepoints across the first 24 hours of menstruation, significantly reduced perceived menstrual pain, compared to placebo. I confirmed that dysmenorrhoeic pain reduces polysomnographic and subjective measures of sleep quality compared with the pain-free follicular phase. I also showed, for the first time, that diclofenac potassium is effective, compared to placebo, in alleviating nocturnal pain, along with restoring subjective sleep quality and polysomnographic measures of objective sleep quality in women with severe primary dysmenorrhoea. My studies have addressed several gaps in the knowledge about primary dysmenorrhoea. I have shown that women with primary dysmenorrhoea are hypersensitive to deep muscle pain, supporting the hypothesis of other researchers that the recurrent menstrual pain experienced by these women is associated with central sensitisation, and may predispose women with primary dysmenorrhoea to other chronic painful conditions. Therefore, limiting the monthly noxious input into the central nervous systems of these women, by means of effective treatment of dysmenorrhoea, may improve their long-term health. The research presented in this thesis further highlights the efficacy of diclofenac potassium in relieving not only day-time and night-time dysmenorrhoeic pain, but also in restoring objective and subjective pain-induced sleep disturbances in women with dysmenorrhoea. Further, my research has shown that dysmenorrhoeic pain has an immediate negative impact on quality of life and mood during menstruation. The results of this thesis show the multi-factorial impact of dysmenorrhoea and should stimulate further research about the long-term benefits of effective treatment of menstrual pain

The effect of a ketogenic diet versus a high-carbohydrate, low-fat diet on sleep, cognition, thyroid function, and cardiovascular health independent of weight loss: study protocol for a randomized controlled trial

Abstract Background Many physiological health benefits observed after following a ketogenic diet (KD) can be attributed to the associated weight loss. The KD has become more prominent as a popular health choice, not only in obese/overweight individuals, but also in healthy adults. The study aims to determine the effects of a KD, independent of weight loss, on various aspects of physiological health including: sleep, thyroid function, cognition, and cardio-metabolic health. The study will also aim to determine whether a change in basal metabolic rate may be associated with any changes observed. Methods Twenty healthy men and women between 18 and 50 years of age will take part in this study. In a randomized controlled, cross-over design, participants will follow two isocaloric diets: a high-carbohydrate, low-fat diet (55% CHO, 20% fat, 25% protein) and a KD (15% CHO, 60% fat, 25% protein). Each dietary intervention will last for a minimum of 3 weeks, with a 1-week washout period in between. Before and after each diet, participants will be assessed for sleep quality, cognitive function, thyroid function, and basal metabolic rate. A blood sample will also be taken for the measurement of cardio-metabolic and immune markers. Discussion The present study will help in understanding the potential effects of a KD on aspects of physiological health in healthy adults, without the confounding factor of weight loss. The study aims to fill a significant void in the academic literature with regards to the benefits and/or risks of a KD in a healthy population, but will also explore whether diet-related metabolic changes may be responsible for the changes observed in physiological health. Trial registration Pan African Clinical Trial Registry ( www.pactr.org ), trial number: PACTR201707002406306 . Registered on 20 July 2017

Additional file 1: of The effect of a ketogenic diet versus a high-carbohydrate, low-fat diet on sleep, cognition, thyroid function, and cardiovascular health independent of weight loss: study protocol for a randomized controlled trial

SPIRIT 2013 fillable checklist indicating the position of recommended items in the manuscript. (DOC 121 kb

Shared mechanisms in stemness and carcinogenesis: lessons from oncogenic viruses

A rise in technologies for epigenetic reprogramming of cells to pluripotency, highlights the potential of understanding and manipulating cellular plasticity in unprecedented ways. Increasing evidence points to shared mechanisms between cellular reprogramming and the carcinogenic process, with the emerging possibility to harness these parallels in future therapeutics. In this review, we present a synopsis of recent work from oncogenic viruses which contributes to this body of knowledge, establishing a nexus between infection, cancer, and stemness